After graduating with a degree in mechanical engineering from the University of Stuttgart, Mezger was hired by Porsche in 1956 and began working in the Experimental Department at Zuffenhausen. He was involved in the development of F2 engines in the late 1950s and then in the design of the 1.5-liter Porsche flat-eight Formula 1 engine which was raced by Dan Gurney and Jo Bonnier in 1962. The project was short-lived but in 1965 Ferdinand Piech, the head of the Experimental Department, decided to create a Motorsport Division and Mezger was named as its head. The company concentrated on sportscar racing with the 904, 906, 908 and 910 models, winning the International Championship for Makes in 1969 and in 1970 and 1971 in the new Porsche 917. There was further success in the United States with success in CanAm and IMSA.
In 1972 the company went public and was reorganized though Mezger remained in charge of racing engine design at the new base in Weissach. In the late 1970s Porsche was dominant in sportscar racing with the 935. In the autumn of 1981 the company was approached by McLaren and asked to build a turbocharged Formula 1 engine. This was funded by TAG and known as the TAG-Porsche. The result was a spectacularly successful engine which enabled McLaren to win the Formula 1 World Championship in 1984-85-86. The engines continued to be used in 1987 but by then they had been eclipsed by Honda.
At the same time, Porsche's success in sportscar racing continued with the 956 and 962 models. In 1987 the company announced plans to compete in CART racing with Al Holbert named to head the program. The program was moderately successful after the company abandoned its own chassis and used March machinery. It came to a close in 1990.
At the same time Mezger and his engineers designed a new V12 Formula 1 engine which, it was announced, would be available to anyone who had the money necessary. Footwork boss Wataru Ohashi came up with the finance but the engine was a disaster and was abandoned by the team in the middle of the 1991 season.